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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1vom
Original Entry
Title:
Muscle protein
Compound:
Myosin
Mutant:
No
UniProt/Swiss-Prot:
P08799-MYS2_DICDI
EC Class:
No EC number available
Other CSA Entries:
Overview of all sites for 1vom
Homologues of 1vom
Entries for UniProt/Swiss-Prot: P08799
Other Databases:
PDB entry: 1vom
PDBsum entry: 1vom
UniProt/Swiss-Prot: P08799
Literature Report:
Introduction:
Myosin is the key enzyme in transducing the energy from ATP hydrolysis into directed movement. Muscle contraction involves the relative movements of myosin and actin filaments. This movement is achieved by the interaction of the globular heads of myosin with actin, and is driven by the hydrolysis of ATP in the myosin head domains.
Mechanism:
Binding of ATP to the active site induces cleft closure with Glu 459 moving to form a salt bridge with Arg 238. The 'lytic' water molecule is released from Arg 238 and positioned for nucleophilic attack on the gamma phosphate by interactions with Ser 237 and with a second water molecule that interacts wih Glu 459 and the backbone oxygen of Gly 457. Departure of the gamma phosphate of ATP from the beta phosphate is promoted by a hydrogen bond from a gamma phosphate oxygen to the backbone NH group of Gly 457; this hydrogen bond forms specifically in the transition state. Attack by the lytic water molecule on the gamma phosphate is promoted by deprotonation of this water by the second water (which ends up as a hydronium ion, one of the reaction products as determined experimentally). Positive charge accumulation on this second water molecule is stabilised by its interactions with Glu 459 and with Gly 457. Accumulation of negative charge on the beta-gamma bridging oxygen as it departs from the gamma phosphate is stabilised by interactions of this atom to the side chain NH2 of Asn 233 and the backbone NH of Gly 182.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYA 182 182Backbone amide
ElectrostaticTransition state
Backbone amide stabilises accumulation of negative charge on the beta-gamma bridging oxygen as this atom departs from the gamma phosphate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15049682 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASNA 233 233Sidechain
ElectrostaticTransition state
Side chain amide stabilises accumulation of negative charge on the beta-gamma bridging oxygen as this atom departs from the gamma phosphate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15049682 Related protein: UniProt P10587 Mutagenesis of residue
PubMed ID 15049682 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYA 457 457Backbone amide, Backbone carbonyl
ElectrostaticWater
ElectrostaticTransition state
Backbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. Backbone O is proposed to interact with and stabilise accumulation of positive charge on the water molecule that deprotonates the lytic water.
Evidence from paper Evidence concerns Evidence type
PubMed ID 15049682 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 9092805 Related protein: UniProt P10587 Mutagenesis of residue
PubMed ID 9092805 Related protein: UniProt P10587 Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA 459 459Sidechain
ElectrostaticWater
Proposed to stabilise accumulation of positive charge on the water molecule that deprotonates the lytic water.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12429851 Related protein: UniProt P10587 Mutagenesis of residue
PubMed ID 9092805 Related protein: UniProt P10587 Conservation of residue
PubMed ID 9092805 Related protein: UniProt P10587 Mutagenesis of residue
PubMed ID 15049682 Current protein Residue is positioned appropriately (ligand position known)
Notes:
Various mechanims that differ from that given here have been proposed, including the involvement of Ser 236 in proton transfer (ref 7619795). The recent proposal of Onishi et al (ref 15049682) has been used for this entry.

In many enzymatic phosphoryl transfer reactions, positively charged ions around the gamma and beta phosphates of ATP have been implicated in stabilising negative charge in the transition state. In the myosin active site, Lys 185 and an Mg2+ ion are present; however the mutation K185A does not abolish catalysis (see ref 15049682). In addition, if the transition state for NTP hydrolysis is dissociative rather than associative in nature, placing positive charges around the gamma phosphate would not be catalytic (see for example Admiraal and Herschlag, Chem Biol. 1995 Nov;2(11):729-39.)
References:
1
On the myosin catalysis of ATP hydrolysis.
H. Onishi and N. Mochizuki and M. F. Morales
Biochemistry 43, (13) 3757-63, (2004).
15049682
2
Functional transitions in myosin: role of highly conserved Gly and Glu residues in the active site.
H. Onishi and M. F. Morales and S. Kojima and K. Katoh and K. Fujiwara
Biochemistry 36, (13) 3767-72, (1997).
9092805
3
Early stages of energy transduction by myosin: roles of Arg in switch I, of Glu in switch II, and of the salt-bridge between them.
H. Onishi and T. Ohki and N. Mochizuki and M. F. Morales
Proc Natl Acad Sci U S A 99, (24) 15339-44, (2002).
12429851
4
X-ray structure of the magnesium(II).ADP.vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution.
C. A. Smith and I. Rayment
Biochemistry 35, (17) 5404-17, (1996).
8611530
5
X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-.
A. J. Fisher and C. A. Smith and J. B. Thoden and R. Smith and K. Sutoh and H. M. Holden and I. Rayment
Biochemistry 34, (28) 8960-72, (1995).
7619795
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